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Biomedical subjects

R E Bulger

Publications and source records attributed to R E Bulger.

At least 19 recordsLinked to original sources
PubMed1994

Toward a statement of the principles underlying responsible conduct in biomedical research.

Biomedical research still does not have clear, written, agreed-upon underlying values (for a number of possible reasons that are discussed), and a variety of new pressures are making it necessary to formulate such principles. Toward that goal, this essay first traces the development of the underlying principles that have been formulated in the sphere of human subjects research, from the ancient Hippocratic injunction of do no harm to the three principles identified in 1979 by the National Commission for Protection of Human Subjects of Biomedical and Behavioral Research: respect for persons; beneficence; and justice. Using these principles as a pattern, the following "candidate principles" are proposed for biomedical research to stimulate discussion and the development of consensus among biomedical scientists: honesty of scientists (which encompasses the essential values of integrity, objectivity, verifiability, and truthfulness); respect for others (including respect for research subjects--both humans and other animals--colleagues, and the environment); scholarly competence (which is related to the processes of obtaining and passing on knowledge); and stewardship of resources (involving obligations to protect society from the problems intertwined with scientific advances). Guiding principles of this type must be articulated so they can be transmitted to upcoming scientists, who then can productively and responsibly help shape the future of the research enterprise.

Animal Experimentation↗
PubMed1993

Studying science in the context of ethics.

The authors describe their experiences in developing and introducing a course on responsible conduct at the Graduate School of Biological Sciences at the University of Texas Health Science Center at Houston. The paper covers issues involved with course faculty, course content and format, and evaluation. At least half of the course time focused on general or case-study discussions of the students and faculty about ethical problems raised in course readings or the students' research experiences. An important issue for institutions trying to encourage students to recognize, reason about, and understand ethical concerns is how the institution itself becomes aware of the ethical implications of its own unconsciously or explicitly stated policies. Such reflection among institutional leaders is critical to fostering the public trust necessary for a profession to sustain its right to self-regulation and its claim of authenticity.

Academic Medical Centers↗
PubMed1991

The role of phosphate in the potentiation or amelioration of acute renal failure.

Alterations in the balance of several cations have been shown to affect the severity of acute renal failure. It has been suggested in both clinical and experimental studies that changes in phosphate balance can markedly potentiate as well as ameliorate the renal dysfunction seen in both acute and chronic nephropathies. To determine the role phosphate plays in the course of gentamicin-induced acute renal failure, we examined rats maintained on control, phosphate-supplemented, and phosphate-depleted diets. In both control and phosphate-supplemented groups of rats, the degree and severity of gentamicin-induced acute renal failure was similar. By contrast, renal function was better preserved in the phosphate-depleted group. Furthermore, morphologic evaluation revealed a significantly lower number of necrotic proximal tubule cells in phosphate-depleted rats when compared to the control or phosphate-replete rats. Renal cortical gentamicin concentrations were not different between the phosphate-depleted and phosphate-supplemented groups. We conclude that phosphate depletion is protective against nephrotoxicity. This effect appears to be independent of alterations in serum calcium, urinary calcium excretion and renal cortical gentamicin concentration.

Acute Kidney Injury↗
PubMed1989

A comparison of the effects of tetraplatin and cisplatin on renal function and gentamicin pharmacology in rats.

Tetraplatin (tetrachloro[d,l-trans]1,2-diaminocyclohexane platinum IV (TTP)) is a new platinum analogue active against L1210 murine leukemia that is resistant to cisplatin (diamminedichloroplatinum II (DDP)). Since nephrotoxicity is a significant problem with DDP therapy, we compared the effects of equitherapeutic doses of TTP and DDP on renal structure and function in rats. We also studied the effects of the 2 platinum compounds on the distribution and excretion of gentamicin (GENT), an antibiotic that is excreted solely by the kidneys. Rats treated intravenously with 2.85 mg/kg of DDP on days 1, 5 and 9 had significantly different plasma urea nitrogen (BUN) levels and creatinine clearance rates on day 16 than those given the same doses of TTP. The renal function of TTP-treated rats did not differ from that of controls or rats given only GENT. Twenty-four hours after a single GENT dose (given on day 15), DDP-treated rats had higher GENT concentrations in the plasma, liver and spleen than rats given GENT alone. TTP-treated rats had higher GENT levels only in the spleen. DDP-treated rats retained a higher percentage of the injected platinum in the renal cortex than those treated with TTP. Light microscopic examination of renal tissue showed necrotic cells and dilated tubules in the proximal tubules of DDP-treated rats while the kidneys of TTP-treated rats were largely indistinguishable from those of controls. Thus, our results indicate that the distribution of platinum in the kidneys differs between rats treated with TTP and those treated with DDP. This may partly explain the considerably lower nephrotoxicity of TTP.

Animals↗
PubMed1989

A comparison of thermal enhancement of cis-diamminedichloroplatinum (II) induced renal and intestinal toxicities by whole body hyperthermia in the rat.

Thermal enhancement of cis-diamminedichloroplatinum (II) (DDP) induced renal and intestinal toxicities by whole body hyperthermia (WBH) were compared using a F344 rat model. Thermal enhancement ratios (TER) for DDP-induced nephrotoxicity were calculated using renal functional assays and morphological techniques. TER values for gastrointestinal (G.I.) toxicity were calculated using "severity of diarrhea" and jejunal crypt cell survival as assays. TER's for renal damage varied between 3 and 3.4, whereas the TER measured for G.I.-toxicity was 1.8. Physiological changes caused by WBH or intrinsic differences in the sensitivities of normal tissues to DDP +/- WBH may be responsible for the differences in thermal enhancement of DDP-induced renal and intestinal toxicities.

Animals↗
PubMed1988

o-(beta-Hydroxyethyl)-rutoside-mediated protection of renal injury associated with cis-diamminedichloroplatinum(II)/hyperthermia treatment.

A bioflavonoid, o-(beta-hydroxyethyl)-rutoside, has been investigated for its potential to increase the therapeutic index of the combined treatment modalities of whole body hypothermia (WBH) (41.5 degrees C) and chemotherapy (cisplatin) in studies utilizing a transplantable fibrosarcoma solid tumor model in Fischer rats. When whole body WBH was induced 45 min after cisplatin administration, a significantly increased tumor growth delay was noted beyond that achieved by either treatment modality alone. The combination of WBH and cisplatin treatments, however, produced an unacceptable increase in renal injury. o-(beta-Hydroxyethyl)-rutoside administration was found to effectively block the renal injury without interfering with the antitumor efficacy of the combined regimen. Potential explanations for the ability of o-(beta-hydroxyethyl)-rutoside to affect the increase in WBH-cisplatin therapeutic regimen are discussed.

Animals↗
PubMed1988

Effect of cis-diamminedichloroplatinum(II) combined with whole body hyperthermia on renal injury.

The effect of whole body hyperthermia (WBH) on cis-diamminedichloroplatinum (II) (DDP) induced renal toxicity and antitumor effect was studied using a F344 rat model. Renal injury at 5 and 14 days after treatment was evaluated using animal mortality, renal functional assays (blood urea nitrogen, creatinine), and histopathological methods. WBH (120 min at 41.5 degrees C) enhanced both antitumor effects and toxic side effects. The latter included increased mortality, increased blood urea nitrogen and creatinine levels, and increased renal damage. After simultaneous treatment with WBH and DDP, thermal enhancement ratios (TER) for renal damage between 2.5 and 3.0 were calculated. The histopathological changes observed in the kidney after DDP alone or combined with WBH were primarily found in the proximal pars recta tubules (S3 segment) in the outer stripe of the outer medulla. There was no qualitative difference in tubular damage between rats treated with DDP alone or those treated with DDP combined with WBH. However, at a fixed DDP dose, damage in the combined treatment modality group was significantly greater than in the DDP-only treated group.

Animals↗
PubMed1987

A comparison of the effects of cisplatin and N-methyliminodiacetato-(1,2-diaminocyclohexane)-platinum(II) on renal function and gentamicin excretion in rats.

N-methyliminodiacetato(1,2-diaminocyclohexane)-platinum(II) (MIDP) is a new third-generation water-soluble antitumor platinum complex. This study compares the effects of MIDP (3 injections of 25 mg/kg each on days 1, 5 and 9) on renal structure and function and the urinary excretion of gentamicin (GENT) with those of a single 6 mg/kg dose of cisplatin (DDP) in F-344 (Fischer) rats. GENT was given as a single dose of 30 mg/kg 7 days after DDP injection or the last MIDP injection. Rats given DDP and GENT had significantly different plasma urea nitrogen (BUN) levels (315 +/- 79 mg/dl) and creatinine clearance (0.40 +/- 0.24 ml/[min.kg]) than did the control group that was given only GENT (15 +/- 1 mg/dl and 5.5 +/- 0.6 ml/[min.kg]). MIDP did not affect renal function (BUN, 16 +/- 3 mg/dl; creatinine clearance, 6.1 +/- 1.0 ml/[min.kg]). Light microscopic examination of renal tissue from MIDP-treated rats did not reveal any evidence of cell degeneration or necrosis. Rats given GENT alone excreted 72 +/- 4% of the dose in 24 h and had plasma gentamicin levels of 19 +/- 2 ng/ml 24 h after injection. The group pretreated with DDP had lower urinary GENT excretion (31 +/- 10%) and higher plasma GENT levels (7491 +/- 3750 ng/ml). MIDP pretreatment had no effect on GENT excretion (72 +/- 8%) or plasma GENT levels (16 +/- 2 ng/ml). Thus, MIDP did not cause any measureable decrease in renal function or GENT excretion in our study. Since nephrotoxicity is a significant problem with DDP administration, further studies with MIDP are warranted.

Animals↗
PubMed1987

Use of animals in experimental research: a scientist's perspective.

The present article was written as an attempt to understand the position of animal rights groups, to stimulate scientists to define their own positions, and to encourage scientists to interpret their use of animals to the rest of society. The article attempts to generate a statement of practices that might be useful in experiments that utilize animals in research. The statement is an extension of the three R's originally proposed by Russell and Burch (W.M.S. Russell and R.L. Burch [1959]: Principles of Humane Experimental Technique, Springfield, IL, Charles C. Thomas) into four R's: refinement, reduction, replacement, and review.

Animal Care Committees↗
PubMed1987

Structural and functional correlates of effects of angiotensin-induced changes in rat glomerulus.

The effects of systemically infused angiotensin II (ANG II) (5, 50, and 100 ng X min-1 X 100 g body wt-1; groups 1, 2, and 3, respectively) were studied in Sprague-Dawley rats. All doses increased systemic blood pressure, fractional excretion of sodium, and urine flow rate but decreased glomerular filtration rate. Scanning electron microscopy revealed no detectable changes in the visceral epithelium or measurable alterations in the total area of endothelial capillary surface occupied by pores. Glomerular basement membrane surface densities of outer (OCG) and inner (ICG) cortical glomeruli averaged 0.22 micron2/micron3 of glomerular tuft volume in all groups. Volume ratios of the individual glomerular tufts to that of their Bowman's capsule of OCG were less (P less than 0.05) in groups 1 and 2 (52 +/- 3 and 63 +/- 9%) than the control group (72 +/- 1%). The volume fraction of the glomerular capillaries to their Bowman's capsules remained approximately 25% in all groups. However, the volume fraction of parenchyma to Bowman's capsule was reduced in group 1 to 30 +/- 4% and 38 +/- 5% in group 2 compared with the control value of 47 +/- 2% (P less than 0.05). Thus ANG II reduced glomerular tuft volume and parenchyma but did not alter filtration surface area or capillary endothelial epithelial surface characteristics.

Angiotensin II↗
PubMed1986

Morphology of norepinephrine-induced acute renal failure in the dog.

The 40-minute infusion of norepinephrine (NE) into the renal artery of dogs produces a reversible ischemic model of acute renal failure. While the physiology of this model has been extensively studied, no complete description of the pathology exists. This study uses light microscopy and transmission electron microscopy to describe and quantitate the structural and ultrastructural changes which occur in the kidneys of dogs 1, 3, and 24 hours after the intrarenal infusion of 0.75 mg/kg/minute of NE. One hour after a 40-minute NE infusion the majority of convoluted and straight proximal tubules showed apical blebs, loss of brush border, microvillar whorl formation, and mitochondrial condensation and high-amplitude swelling with flocculent densities. Necrotic cells were occasionally seen at 1 hour. The injury was progressive after 3 hours and by 24 hours animals had either complete or partial patchy necrosis of all regions of the proximal tubule. The percentages of injured and necrotic proximal tubules in outer, mid-, and inner cortical regions are presented. We conclude that the extent and pattern of injury seen after NE infusion differs significantly from the renal artery clamping model of ischemia.

Acute Kidney Injury↗